The hypothesis of the current proposal is that near parturition, glucocorticoids (GCs) reduce uterine-placental adherence by suppressing the synthesis of fibronectin (FN) and other extracellular matrix (ECM) proteins of cells in placenta and fetal membranes and/or by limiting the ability of these cells to adhere to ECM components. Preliminary data demonstrate that GCs nearly completely suppress the synthesis of FN and other ECM proteins in primary cultures of human cytotrophoblasts and amnion epithelial cells. To determine the effects of GCs on the ability of these cells to synthesize ECM proteins, in proposed experiments, the effects of GCs on levels of FN, laminin, collagens I, III, and IV in cytotrophoblasts and amnion cells will be evaluated using ELISA, Western and Northern blotting and immunoprecipitation procedures. Immunohistochemical and in situ hybridization techniques will be used to identify cells in placenta and fetal membranes expressing specific ECM proteins and their mRNAs. Assays of ECM protein mRNA synthesis and degradation will be used to elucidate a molecular mechanism for the GC inhibition of matrix protein expression in cytotrophoblasts and amnion cells. The effect of GCs on integrin (i.e. receptors for ECM proteins) expression and adhesive properties of cells will be determined in surface-labeling and cell attachment studies. To test the hypothesis that labor is associated with alterations in ECM protein expression in the placenta and fetal membranes, the levels of ECM proteins in placental and membranous tissue obtained from human pregnancies with and without labor will be compared. Since it is not feasible to monitor levels of placental and membrane ECM proteins during labor in humans, ECM protein expression will also be examined in tissues obtained from rhesus monkeys before labor, during labor, and following delivery of the fetus. In addition, to dissect the regulation of ECM protein expression in placenta and fetal membranes by paracrine effectors associated with parturition, the individual and combined effects of GCs, interleukin-6, and estradiol on ECM protein levels in human and rhesus monkey placental and fetal membrane cells will be tested. Based on proposed studies we will establish a role of GCs in the genesis of the requiste changes in ECM protein expression in placenta and fetal membranes at parturition.